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The Chemistry Experiment -- Augmentation

When I began The Chemistry Experiment, there were about twenty options out there for me to try.  I was a wuss and quit at six.  I said "no" to a fifth SSRI/SNRI, and rejected the whole class of MAOIs (Monoamine Oxidase Inhibitors) -- which were just too tempting to use as a backup plan.  Instead I headed east, and Chinese herbs got me through almost two years.  Later I returned to an antidepressant that hadn't been effective before, but at least it did no harm.  This time it helped.  Was this because I was taking Xiao Yao San as well?  Who knows.  But now it doesn't work any more anyway.

Meanwhile, there is a new strategy called augmentation.  If one med doesn't work, try combining two, an antidepressant with an anti-psychotic, anti-convulsant, mood stabilizer, atypical anti-psychotic.  Suddenly the number of possibilities is up to forty.  That doesn't actually give you 1600 potential combinations, because if you combine MAOIs with most of the others, it'll kill you.  Most days, that doesn't seem like a good thing. Anyway, the number of potential trials has increased exponentially, and I am nowhere near the end of the chemistry experiment.

My doctor gave me five possibilities to augment my current nortriptyline, because she figured I would reject three out of hand.  What is really sad is to be in a such a state that I am giving any of her suggestions serious thought at all.

The National Institute of Mental Health did a major study about five years ago, trying to find the best approach for treating treatment-resistant depression.  All those wonderful success stories you see on tv, the woman skipping on the beach, the man dancing with his wife, are from trials using mild or moderately depressed people who have not been on meds before.  While half of those who take antidepressants achieve remission with their first or second med, and another 10% get at least some relief, the odds fall dramatically after that.  STAR*D (Sequenced Treatment Alternatives to Treat Depression) used six antidepressants and four augmentation strategies, as well as Cognitive Behavioral Therapy, in four sequenced trials for people who had already been treated unsuccessfully with a seventh antidepressant, to try to determine the most effective options.

As it happens, I took four of the six during the same time frame as the study.  And three of my doctor's augmentation suggestions were on the STAR*D list.  So this time, I know the odds.

For example, at the third trial (fourth, counting the unsuccessful med that qualified participants for the study) 15.9% of those who augmented with Lithium achieved remission.  On the other hand, 23.2% had to quit because they couldn't tolerate the side effects.  Lots more had some side effects, but they were intolerable for only a quarter of the participants.  The numbers for T(3), a thyroid medication were 24.7% help and 9.6% intolerable.  So those are my odds for two out of my doctor's five.

A side note: in the fourth trial, comparing an MAOI to an Effexor/Remeron cocktail, remission rates were down to 6.9% and 13.7%.  Withdrawal because of harm rates were 41.4% and 21.6%.  They called those results modest.  My first rule -- if the odds of harm exceed the odds of help, give it a pass.

The results of the STAR*D Study in a nutshell -- the more meds you have to try, the lower your odds of positive results.  They found there is little to recommend one strategy over another, other than by the amount of harm they cause.

There is a major piece of information missing from this $35,000,000 study.  What is the placebo rate?  A few years into a disease that remits without treatment, the rates of remission were low enough to suggest the question -- were the meds preventing remission?  At least the question occurred to me.  To my knowledge, it has not been addressed in the literature.

They didn't use placebos.  So we don't know.  Placebos might have provided clues as to whether the meds made people worse.  But they figured it was unethical not to treat people this sick.  But placebo is a treatment.  I read in The Carlat Psychiatry Report, "in one study that looked at all antidepressant studies submitted to the FDA from 1987 to 1997, the placebo effect was shown to account for 75% of all improvement on active treatment (Khan et al, Arch Gen Psychiatry 2000;57:311-317)."  I, for one, would have volunteered for the placebo!  More on placebos next week...

Remembering The Cure from last week, I have been considering other possibilities, beyond that list of five.  I think Peeps would be a good augmentation for nortriptyline, the simple, well-tested, in and out of microwaves, and much beloved option paired with the plain, old-fashioned tricyclic that comes in generic and never did me any harm.  The starter dose would be the original, your basic yellow chick.  And you wondered when I would get to it, didn't you?!  But Peeps provides other dosage levels, as well, as pictured here.

In fact, like Abilify, Peeps not only increases your blood sugar, but also is a very versatile product.  There are options for comorbidity issues, such as:

-- eating disorders

--personality disorders

-- impulse control disorder

and borderline personality disorder.  I understand this peep may get a new diagnosis in the much debated and eagerly anticipated DSM-V, at which publication, I will have to edit this post.

And then there are your psychotic features.  Oh dear, is Peeps the appropriate medication to treat psychotic features?  Or are psychotic features a side effect of Peeps?  As with most neurological medications, flip a coin.  And while you are at it, expect psychotic features to be a side effect of discontinuation!

flair from


  1. Your blog IS the best medicine. I am still laughing!

    Have you ever considered a one woman show? This stuff is too funny to have such a limited audience.

    I am picturing the pharmacy shelves filled with different colored Peeps. "Well Ms. Jones what can I get for you today? Oh I see your doctor has ordered the blue peeps for you. You will find these especially helpful. Now make sure you hide them from your granddaughter! We don't want a repeat of last month with the pink Peeps, now do we?"

    The possibilities are endless!


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